The proposed research includes the elucidation of the processes involved in the regulation of protein synthesis by NAD, 2'dNAD, and AMP. We have clearly demonstrated that AMP (25 micrometers to 2 mM) inhibits polypeptide synthesis in lysed rabbit reticulocytes in the presence of either an ATP generating system or with ATP (1mM) alone. This inhibition of polypeptide synthesis can be restored by the enzymatic removal of AMP. The proposed studies are designed to determine if AMP inhibits the initiation or elongation process. Included is the regulation of protein synthesis as a continuation of studies on the effect of sugar phosphates on the concentrations of the low molecular weight (2',5') oligoadenylate, (2',5') pppA (pA)n, its cordycepin analog (2',5') ppp3'dA(p3'dA), and their corresponding core nucleotides in lysed rabbit reticulocytes, lymphocytes, HeLa cells and DNA-defective mammalian cells. The protein synthesis, (2',5') oligoadenylate, and 3'-deoxy (2',5') oligoadenylate studies will be coordinated with the effect of the core (2',5') oligonucleotides with and without interferon on poly (ADP-ribosylation) of histone and non-histone proteins in HeLa cells, lymphocytes, and DNA repair defective cells as related to the transformation of cells and viral infectivity. Finally, experiments will be continued to determine if increased concentrations of 2'dATP in HeLa cells will result in the synthesis of 2'dNAD. 2'dNAD has been reported from this laboratory to differ markedly from NAD in its effect on DNA repair following the ADP-ribosylation of non-histone proteins in nuclei isolated from HeLa cells and rat liver.